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https://www.readbyqxmd.com/read/28431230/structural-basis-for-guide-rna-processing-and-seed-dependent-dna-targeting-by-crispr-cas12a
#1
Daan C Swarts, John van der Oost, Martin Jinek
The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28421167/iron-and-virulence-in-francisella-tularensis
#2
REVIEW
Girija Ramakrishnan
Francisella tularensis, the causative agent of tularemia, is a Gram-negative bacterium that infects a variety of cell types including macrophages, and propagates with great efficiency in the cytoplasm. Iron, essential for key enzymatic and redox reactions, is among the nutrients required to support this pathogenic lifestyle and the bacterium relies on specialized mechanisms to acquire iron within the host environment. Two distinct pathways for iron acquisition are encoded by the F. tularensis genome- a siderophore-dependent ferric iron uptake system and a ferrous iron transport system...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28418764/disease-surveillance-of-california-ground-squirrels-spermophilus-beecheyi-in-a-drive-through-zoo-in-oregon-usa
#3
Julia Ter Beest, Andrew Cushing, Modesto McClean, Wendy Hsu, Robert Bildfell
Rodents and other small wild mammals are often considered to be pests and vectors for disease in zoos that house small populations of valuable threatened and endangered animals. In 2005, three nonhuman primates at a drive-through zoo in Oregon, USA, acquired tularemia from an unknown source. Due to an abundance of California ground squirrels ( Spermophilus beecheyi ) on zoo grounds, we instituted serosurveillance of this species from July through September 2008 to determine the prevalence of antibodies against pathogens considered to be potentially transmissible to collection animals...
April 18, 2017: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/28405072/tularemia-presenting-as-pulmonary-nodules-in-an-immunocompromised-patient
#4
Tony Alias, Mohammad Kazem Fallahzadeh, Mezgebe Berhe
Tularemia is a zoonotic disease caused by Francisella tularensis that can be transmitted to humans when they handle rabbits, receive tick bites, consume contaminated water, or inhale aerosolized particles. We present the case of a 51-year-old white man with rheumatoid arthritis who was taking immunosuppressive medications and presented with tularemia. Our patient acquired the typhoidal form of tularemia, which is a severe systemic illness that manifests with fevers, headaches, myalgias, vomiting, diarrhea, and neurological symptoms, due to his immunocompromised state...
April 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28402703/molecular-detection-of-francisella-spp-among-ticks-attached-to-camels-in-egypt
#5
Nahed H Ghoneim, Khaled A Abdel-Moein, Hala M Zaher
This study was conducted to investigate the possible role of camels and attached ticks in the epidemiology of Francisella spp. including Francisella tularensis. For this purpose, a total of 319 ticks (248 Hyalomma dromedarii and 71 Amblyomma spp.) as well as 100 blood and 50 fecal samples collected from camels were screened for the presence of Francisella spp. by PCR through amplification of Francisella 16S rRNA gene. Positive samples were then tested for F. tularensis by PCR. In addition, serum samples from 75 camel abattoir workers were examined for the presence of IgG antibodies against F...
April 12, 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28401066/importance-of-metabolic-adaptations-in-francisella-pathogenesis
#6
REVIEW
Jason Ziveri, Monique Barel, Alain Charbit
Francisella tularensis is a highly infectious Gram-negative bacterium and the causative agent of the zoonotic disease tularemia. This bacterial pathogen can infect a broad variety of animal species and can be transmitted to humans in numerous ways with various clinical outcomes. Although, Francisella possesses the capacity to infect numerous mammalian cell types, the macrophage constitutes the main intracellular niche, used for in vivo bacterial dissemination. To survive and multiply within infected macrophages, Francisella must imperatively escape from the phagosomal compartment...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28398677/preparing-for-biological-threats-addressing-the-needs-of-pregnant-women
#7
REVIEW
Amelia K Watson, Sascha Ellington, Christina Nelson, Tracee Treadwell, Denise J Jamieson, Dana M Meaney-Delman
Intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. We review what is known about the maternal and fetal effects of seven biological threats: Bacillus anthracis (anthrax); variola virus (smallpox); Clostridium botulinum toxin (botulism); Burkholderia mallei (glanders) and Burkholderia pseudomallei (melioidosis); Yersinia pestis (plague); Francisella tularensis (tularemia); and Rickettsia prowazekii (typhus)...
March 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28387220/targeted-activation-of-diverse-crispr-cas-systems-for-mammalian-genome-editing-via-proximal-crispr-targeting
#8
Fuqiang Chen, Xiao Ding, Yongmei Feng, Timothy Seebeck, Yanfang Jiang, Gregory D Davis
Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner...
April 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28377902/role-of-glycosylation-deglycolysation-processes-in-francisella-tularensis-pathogenesis
#9
REVIEW
Monique Barel, Alain Charbit
Francisella tularensis is able to invade, survive and replicate inside a variety of cell types. However, in vivo F. tularensis preferentially enters host macrophages where it rapidly escapes to the cytosol to avoid phagosomal stresses and to multiply to high numbers. We previously showed that human monocyte infection by F. tularensis LVS triggered deglycosylation of the glutamine transporter SLC1A5. However, this deglycosylation, specifically induced by Francisella infection, was not restricted to SLC1A5, suggesting that host protein deglycosylation processes in general might contribute to intracellular bacterial adaptation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28373354/a-protective-role-for-macrophages-in-respiratory-francisella-tularensis-infection
#10
Donald J Steiner, Yoichi Furuya, Michael B Jordan, Dennis W Metzger
Francisella tularensis causes lethal pneumonia following infection of the lungs by targeting macrophages for intracellular replication; however, macrophages stimulated with interferon gamma (IFN-γ) can resist infection in vitro We therefore hypothesized that the protective effect of IFN-γ against F. tularensisin vivo requires macrophages receptive to stimulation. We found that lethality of pulmonary F. tularensis LVS infection was exacerbated under conditions of alveolar macrophage depletion, and in mice with a macrophage-specific defect in IFN-γ signaling (MIIG) mice...
April 3, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28372827/expansion-and-retention-of-pulmonary-cd4-t-cells-after-prime-boost-vaccination-correlates-with-improved-longevity-and-strength-of-immunity-against-tularemia
#11
Lydia M Roberts, Tara D Wehrly, Deborah D Crane, Catharine M Bosio
Francisella tularensis subsp. tularensis strain SchuS4 (Ftt) is a highly virulent intracellular bacterium. Inhalation of 10 or fewer organisms results in an acute and potentially lethal disease called pneumonic tularemia. Ftt infections occur naturally in the U.S. and Ftt was developed as a bioweapon. Thus, there is a need for vaccines that protect against this deadly pathogen. Although a live vaccine strain of Francisella tularensis (LVS) exists, LVS fails to generate long-lived protective immunity against modest challenge doses of Ftt...
March 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28360906/efficacy-of-resistance-to-francisella-imparted-by-ity-nramp-slc11a1-depends-on-route-of-infection
#12
Daniel A Powell, Jeffrey A Frelinger
Natural resistance-associated macrophage protein (NRAMP) encoded by the Slc11a1 gene is a membrane-associated transporter of divalent metal ions. Murine Slc11a1 has two known alleles, a functional Slc11a1(Gly169), which is found in DBA2/J, NOD/LtJ, and 129p3/J and related mouse strains, and a non-functional Slc11a1(Asp169), that is found in C56Bl/6J (B6) and BALB/cJ mice. B6 mice congenic for Slc11a1(Gly169) (B6-Slc11a1(G169) ) are markedly resistant to the intracellular pathogens Salmonella, Leishmania, and Mycobacterium tuberculosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28357328/francisella-iglg-protein-and-the-duf4280-proteins-paar-like-proteins-in-non-canonical-type-vi-secretion-systems
#13
COMMENT
Claire Lays, Eric Tannier, Thomas Henry
Type VI secretion systems (T6SS) are bacterial molecular machines translocating effector proteins into target cells. T6SS are widely present in Gram-negative bacteria where they predominantly act to kill neighboring bacteria. This secretion system is reminiscent of the tail of contractile bacteriophages and consists of a contractile sheath anchored in the bacterial envelope and an inner tube made of stacks of the Hcp protein. The Hcp tube is capped with a VgrG trimer and a spike protein termed PAAR, which acts as the membrane-puncturing device...
October 29, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28348839/long-range-dispersal-moved-francisella-tularensis-into-western-europe-from-the-east
#14
Chinmay Dwibedi, Dawn Birdsell, Adrian Lärkeryd, Kerstin Myrtennäs, Caroline Öhrman, Elin Nilsson, Edvin Karlsson, Christian Hochhalter, Andrew Rivera, Sara Maltinsky, Brittany Bayer, Paul Keim, Holger C Scholz, Herbert Tomaso, Matthias Wittwer, Christian Beuret, Nadia Schuerch, Paola Pilo, Marta Hernández Pérez, David Rodriguez-Lazaro, Raquel Escudero, Pedro Anda, Mats Forsman, David M Wagner, Pär Larsson, Anders Johansson
For many infections transmitting to humans from reservoirs in nature, disease dispersal patterns over space and time are largely unknown. Here, a reversed genomics approach helped us understand disease dispersal and yielded insight into evolution and biological properties of Francisella tularensis, the bacterium causing tularemia. We whole-genome sequenced 67 strains and characterized by single-nucleotide polymorphism assays 138 strains, collected from individuals infected 1947-2012 across Western Europe. We used the data for phylogenetic, population genetic and geographical network analyses...
December 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28348802/cat-bite-induced-francisella-tularensis-infection-with-a-false-positive-serological-reaction-for-bartonella-quintana
#15
Evelina Petersson, Simon Athlin
Introduction. Tularaemia is caused by infection with Francisella tularensistransmitted via direct contact with an infected hare carcass or indirectly through the bites of vectors, but may be cat-bite-associated as well. Medical history and reliable diagnostic analysis are important in order to differentiate it from other cat-associated infections, e.g. Bartonella spp. Casepresentation. A healthy 56-year-old man was examined because of a cat-bite-associated ulceroglandular wound on his right thumb. Nineteen days after the cat bite occurred, a serology test was positive for anti-Bartonella quintana, but negative for anti-F...
February 2017: JMM Case Reports
https://www.readbyqxmd.com/read/28345580/differential-roles-of-caspase-1-and-caspase-11-in-infection-and-inflammation
#16
Si Ming Man, Rajendra Karki, Benoit Briard, Amanda Burton, Sebastien Gingras, Stephane Pelletier, Thirumala-Devi Kanneganti
Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. "ICE(-/-)" or "Casp1(-/-)" mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336603/high-quality-draft-genome-sequence-of-francisella-tularensis-subsp-holarctica-strain-08t0073-isolated-from-a-wild-european-hare
#17
Anne Busch, Prasad Thomas, Kerstin Myrtennäs, Mats Forsman, Silke Braune, Martin Runge, Herbert Tomaso
Here, we report a high-quality draft genome sequence of Francisella tularensis subsp. holarctica strain 08T0073, isolated from the cadaver of a wild European hare (Lepus europaeus) found near Helmstedt, Lower Saxony, Germany, in 2007. In Germany, infected hares are a major source of tularemia in humans.
March 23, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28331079/characterization-and-vaccine-potential-of-membrane-vesicles-produced-by-francisella-noatunensis-sup-orientalis-in-an-adult-zebrafish-model
#18
Leidy Lagos, Julia I Tandberg, Urska Repnik, Preben Boysen, Erik Ropstad, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen
Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. Francisella noatunensis subspecies orientalis (Fno) are Gram-negative, facultative intracellular bacteria that cause the disease francisellosis in fish. Francisellosis is commonly characterized as a chronic granulomatous disease with high morbidity and can result in high mortality depending on the host...
March 22, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28328947/a-spontaneous-mutation-in-kdsd-a-biosynthesis-gene-for-3-deoxy-d-manno-octulosonic-acid-occurred-in-a-ciprofloxacin-resistant-strain-of-francisella-tularensis-and-caused-a-high-level-of-attenuation-in-murine-models-of-tularemia
#19
Taylor Chance, Jennifer Chua, Ronald G Toothman, Jason T Ladner, Jonathan E Nuss, Jo Lynne Raymond, Fabrice V Biot, Samandra Demons, Lynda Miller, Stephanie Halasohoris, Sherry Mou, Galina Koroleva, Sean Lovett, Gustavo Palacios, Nicholas J Vietri, Patricia L Worsham, Christopher K Cote, Todd M Kijek, Joel A Bozue
Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, is the causative agent of tularemia and able to infect many mammalian species, including humans. Because of its ability to cause a lethal infection, low infectious dose, and aerosolizable nature, F. tularensis subspecies tularensis is considered a potential biowarfare agent. Due to its in vitro efficacy, ciprofloxacin is one of the antibiotics recommended for post-exposure prophylaxis of tularemia. In order to identify therapeutics that will be efficacious against infections caused by drug resistant select-agents and to better understand the threat, we sought to characterize an existing ciprofloxacin resistant (CipR) mutant in the Schu S4 strain of F...
2017: PloS One
https://www.readbyqxmd.com/read/28325762/a-genetic-screen-reveals-that-synthesis-of-1-4-dihydroxy-2-naphthoate-dhna-but-not-full-length-menaquinone-is-required-for-listeria-monocytogenes-cytosolic-survival
#20
Grischa Y Chen, Courtney E McDougal, Marc A D'Antonio, Jonathan L Portman, John-Demian Sauer
Through unknown mechanisms, the host cytosol restricts bacterial colonization; therefore, only professional cytosolic pathogens are adapted to colonize this host environment. Listeria monocytogenes is a Gram-positive intracellular pathogen that is highly adapted to colonize the cytosol of both phagocytic and nonphagocytic cells. To identify L. monocytogenes determinants of cytosolic survival, we designed and executed a novel screen to isolate L. monocytogenes mutants with cytosolic survival defects. Multiple mutants identified in the screen were defective for synthesis of menaquinone (MK), an essential molecule in the electron transport chain...
March 21, 2017: MBio
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